Platelet activation is believed to play a role in the pathophysiology of coronary artery disease. To determine whether diseased epicardial or small vessel coronary arteries create conditions that activate platelet, we measured platelet aggregation in 25 patients with large vessel coronary artery disease, 14 patients with microvascular angina and 6 normals. We measured platelet hyperreactivity by impedance aggregometry, a technique that looks at the tendency the platelets have that clump together in whole blood. In our first study we found that platelets that pass through an atherosclerotic bed during rapid atrial pacing become hyperreactive compared to platelets that pass through a normal coronary bed, also during rapid atrial pacing. In a second study we found that maximum upright exercise causes a systemic increase in platelet reactivity in 10 patients with coronary artery disease and 5 patients with chest pain and normal coronary arteries. The platelet hyperreactivity in the two situations described above, through platelet induced spasm or platelet plugs in the coronary circulation, both decreasing blood supply to the myocardium, may contribute to ischemia.